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Biomedical subjects

K Adachi

Publications and source records attributed to K Adachi.

At least 127 records · Page 7Linked to original sources

Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa.

Prostaglandin E2 (PGE2) plays an important role in the regulation of gastric mucus secretion. We have previously shown that the prostaglandin EP4 receptor (EP4) gene is abundantly expressed in gastric mucus-producing cells. Furthermore, we have shown that EP4 is present in a rat normal gastric mucosal cell line (RGM1) and that PGE2 increases mucus secretion from these cells via EP4. Rebamipide, an anti-gastric ulcer agent, has been reported to promote gastric PGE2 production and mucus secretion. However, it is unclear whether rebamipide influences mucus secretion by altering expression of the EP4 gene. Therefore, we tested the effect of rebamipide on EP4 gene expression in the gastric mucosa. Seven-week-old Wistar rats received oral rebamipide (100 mg/kg) with and without water-immersion restraint stress (WRS). All rats were killed, and their gastric tissues were used to investigate the expression of mRNA for EP4 and cyclooxygenase types 1 and 2. The thickness of the gastric mucus layer was also measured. The effect of rebamipide on EP4 gene expression and PGE2 production in RGM1 cells was also investigated in vitro. Furthermore, the effect of PGE2 on cyclic adenosine monophosphate (cAMP) production by RGM1 cells with or without rebamipide was studied. Oral rebami-pide significantly increased EP4 gene expression in the gastric antrum but not in the corpus after WRS. Furthermore, it increased surface mucus thickness and suppressed ulcer formation in the gastric mucosa after WRS. In vitro, rebamipide significantly augmented EP4 gene expression in RGM1 cells, and PGE2 significantly increased the cAMP production by RGM1 cells incubated with rebamipide. Rebamipide promotes EP4 gene expression and may consequently increase the gastric mucus secretion via EP4 receptors in the rat antral mucosa.

Alanine↗

Site-dependent production of transforming growth factor beta1 in colonic mucosa: its possible role in tumorigenesis of the colon.

Transforming growth factor (TGF) beta1 has an antitumorigenic role in the gastrointestinal tract and may be associated with the development of colon neoplasia. In the present study we investigated whether TGF-beta1 production in mucosa is lower in the distal colon, which is where clinical evidence shows that the incidence of colon neoplasia is higher, and whether TGF-beta1 levels were lower in the mucosa of patients with colon adenoma. Production of colon mucosa TGF-beta1 was investigated by means of a 24-hour organ culture with biopsy specimens taken from different segments of the colon of 58 normal subjects by using an enzyme immunoassay. TGF-beta1 production in colon mucosa from locations near the site of sporadic adenoma was also investigated in 46 patients. TGF-beta1 production gradually increased from the rectum to the ascending colon in a statistically significant manner in both normal (r = 0.77, P < .0001) and adenoma-bearing (r = 0.8, P < .0001) mucosa. When TGF-beta1 production was compared between normal and adenoma-bearing mucosa, levels were lower in the latter, although statistically significant results were seen only in the transverse colon (P < .05). TGF-beta1 production has clear site dependency, being lowest in the rectum and highest in the ascending colon. Furthermore, low levels of TGF-beta1 are associated with the development of adenoma. Our results suggest the possibility that this site dependency is associated with the higher epidemiologic incidence of colon neoplasia in the distal colon.

Actins↗

Thyrotropin-releasing hormone and its receptor in the cerebellum of inferior olive destroyed rat brain.

To study the pathophysiology of olivopontocerebellar atrophy (OPCA), we destroyed inferior olive nuclei of male Wistar rats using 3-acetyl pyridine (3-AP) + harmaline + niacinamide. These rats showed a sluggish and ataxic gait. To elucidate the relationship between thyrotropin releasing hormone (TRH) in the Purkinje cell of cerebellum and the inferior olive nucleus, we investigated the concentrations of TRH in the cerebellar cortex, nuclei, and medulla oblongata including the inferior olive nuclei using radioimmunoassay method as well as TRH receptor in the Purkinje cells of cerebellum using immunohistochemical method. All statistical comparisons were done using non-parametric tests (Mann-Whitney U-test). We found that two weeks after the treatment, TRH concentrations in the cerebellar cortex as well as nuclei were significantly lower than in the controls but no significant difference in the medulla oblongata was observed between 3-AP treated rats and controls. Moreover, four weeks after the treatment, TRH-receptor positive Purkinje cell counts were significantly fewer than in the controls. These results suggest that TRH in the Purkinje cell of cerebellum may play a role in the ataxic gait observed in the rats whose inferior olive were destroyed.

Animals↗

beta-cyanoalanine production by marine bacteria on cyanide-free medium and its specific inhibitory activity toward cyanobacteria.

In screening the culture broth of marine bacteria collected at Yap (Micronesia), Palau (Belau), and Okinawa (the southwest islands of Japan) for antimicroalgal activity, 37 out of 2,594 bacterial isolates tested were found to produce anticyanobacterial substances against Oscillatoria amphibia NIES-361. One strain, C-979, identified as a Vibrio sp., was selected and cultured in 2.4 liters of marine broth 2216 to identify the bioactive compound produced by the strain. The purified very hydrophilic compound (16.4 mg) was determined to be beta-cyano-L-alanine (L-CNAla) by instrumental analyses and the application of the advanced Marfey method. L-CNAla did not inhibit the growth of bacteria, yeast, or eukaryotic microalgae, but some cyanobacteria were found to be sensitive to L-CNAla at a concentration of 0.4 to 25 microg/ml. The effect of L-CNAla on some other environmental organisms, including invertebrates and a macroalgae, is discussed. CNAla production in marine broth was examined by thin-layer chromatography for the 37 bacterial isolates which produced an anticyanobacterial substance. The broth of 36 of these strains contained CNAla, suggesting the wide distribution of CNAla production by marine bacteria. This is the first report on bacteria that produce CNAla without a supply of the cyanide ion in the medium.

Alanine↗

Inhibition of binding of E- and P-selectin to sialyl-Lewis X molecule suppresses the inflammatory response in hypersensitivity pneumonitis in mice.

The carbohydrate structure of sialyl-Lewis X (SLe(x)) can function as a ligand for E- and P-selectin, which play important roles in mediating the initial interactions of leukocytes with the endothelium in inflammatory responses. In this study we evaluated the effects of inhibiting E- and P-selectin function with the SLe(x) molecule on the inflammatory response in an experimental murine model of hypersensitivity pneumonitis (HP). Antigen exposure induced marked interstitial and especially perivascular and peribronchiolar infiltration with lymphocytes and granuloma formation, in murine lung sensitized with Saccaropolyspora rectivirgula. These pathologic changes were significantly suppressed with SLe(x) ganglioside analogues through a reduction in the numbers of lymphocytes in bronchoalveolar lavage fluid, as evidenced by the lung index and histologic scores indicating the severity of the inflammatory response. Using specific antibodies, we also evaluated the immunohistochemical localization of SLe(x) in mononuclear cells in granulomas, and of E- and P-selectin in vascular endothelium. Our findings suggest that the molecular interaction between SLe(x), and E- and P-selectin mediates lymphocyte recruitment into the lung parenchyma, which is critical for the inflammatory response in experimental murine models of HP.

Alveolitis, Extrinsic Allergic↗

Optimal scaling of a longitudinal choice variable with time-varying representation of individuals.

A new method of homogeneity analysis is proposed for analysing the repeated measurements of n individuals' choices among m categories. In this method, time-varying scores are assigned to each individual, while time-invariant ones are assigned to each category. For obtaining such scores, a requirement of homogeneity for time-varying individual scores is introduced in addition to the individual-category homogeneity requirement underlying the existing homogeneity analysis. The loss function based on these two requirements is minimized under a suitable normalization condition. This minimization is explicitly attained through eigen-value decomposition, and the graphical representation of the resulting scores allows us to easily find the longitudinal changes in individuals and the relationships among categories.

Choice Behavior↗

Histopathological study of the effects of a single intratracheal instillation of surface active agents on lung in rats.

Pulmonary drug administration of most peptide/protein drugs is characterized by low bioavailability due to low permeability. Surface active agents have been tested as an absorption enhancer, but few studies have been carried out on the local toxicity of these additives. In the present study, to clarify the toxic effects of surface active agents on the lung, a relatively high concentration (1%) of polyoxyethylene 9 lauryl ether (Laureth-9) and sodium glycocholate (SGC) was given to rats in a single intratracheal instillation (100 microliters/rat), and the lung was evaluated histopathologically. In the rats treated with Laureth-9, lung lesions were observed in the bronchi to alveoli. At 1 day after administration, edema, hemorrhage and inflammatory cell infiltration due to degeneration and desquamation of epithelium were observed. At 3 and 7 days after administration, the wound healing process resulting from the lung injury, such as hyperplasia of epithelium and sporadic fibrosis, was noted. SGC also induced lung lesions with a similar histopathological nature, whereas the lesions were mostly confined to the alveoli. These results suggest that surface active agents induce acute inflammation of the lung by intratracheal instillation, that the distribution of lesions is different among surface active agents, and moreover that pathological examination is indispensable for clarifying local toxicity of absorption enhancers in pulmonary drug-delivery studies.

Absorption↗

High incidence of acute myositis with type A influenza virus infection in the elderly.

We describe six elderly cases of acute myositis with type A influenza virus infection (Sydney) during the 1998-1999 outbreak. All six cases suffered from myalgia or muscle weakness especially in the lower extremities and the serum creatine kinase (CK) values were elevated above 1,000 IU/l without MB isoenzymes or electrocardiogram abnormalities. There have been a few case reports of acute myositis associated with influenza virus infection in the elderly. However, we noticed a high incidence of acute myositis among elderly patients with type A influenza virus infection. This complication may occur more commonly in elderly patients than has previously been thought.

Acute Disease↗

Allele frequency of human endothelial nitric oxide synthase gene polymorphism in abdominal aortic aneurysm.

OBJECTIVE: This study was performed to examine the role of the endothelial constitutive NO synthase (ecNOS) gene in patients with abdominal aortic aneurysm (AAA). METHODS: We determined the distributions of polymorphism in intron 4 of the ecNOS (ecNOS4) gene, amplified by polymerase chain reaction, and compared the allele frequencies between subjects with abdominal aortic aneurysms (AAAs) and healthy individuals. PATIENTS: Fifty-eight patients with AAAs and 410 race-matched healthy controls were studied. RESULTS: Two alleles of the ecNOS4 gene, containing 4 (a-allele) and 5 (b-allele) repeats, were identified. We found that the a-allele frequency of this gene was significantly higher in the surgical than in the non-surgical group. CONCLUSION: The results of this study suggest that the a-allele of the ecNOS4 gene is indicative of the need for surgery for AAA. Analysis of the alleles of the ecNOS4 gene polymorphism could provide useful information concerning the clinical course of AAA progression.

Aged↗

Spontaneous regression of a germinoma in the pineal body after placement of a ventriculoperitoneal shunt.

The authors report a case in which a germinoma in the pineal body displayed spontaneous regression after placement of a ventriculoperitoneal (VP) shunt. Spontaneous regression of malignant tumors is extremely rare, occurring in only one of 60,000 to 100,000 patients. Although in rare cases spontaneous regression is known to occur in patients with testicular seminomas, only one case of spontaneous regression of a primary pineal germinoma has so far been reported. In the present case a 17-year-old man presented with headache. A tumor in the pineal body and acute hydrocephalus were revealed by head computerized tomography (CT) and magnetic resonance (MR) imaging, and VP shunt placement was performed. Computerized tomography scanning of the head was performed four times during a 2-week period following the operation, and the patient was temporarily discharged to return to school. At the time of discharge, CT scanning demonstrated no change in the size of the tumor. Two months later, the patient was readmitted to the hospital to undergo surgery. At that time, head MR imaging revealed regression of the tumor. The pathological diagnosis of the lesion was germinoma. The patient underwent three courses of chemotherapy, during which carboplatin and etoposide were administered, in addition to a 24-Gy dose of radiotherapy. No manifestations of nerve impairment were noticed, and the patient was observed on an outpatient basis. The authors think that the factors involved in tumor regression included the effects of the VP shunt, the effects of radiation absorbed during head CT scanning, and the role of the patient's own immune response. However, no conclusion has been reached concerning the actual cause.

Adolescent↗

[Efficacy of methylprednisolone pulse and mild hypothermia therapies in patients with acute encephalopathy].

Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.

Acute Disease↗

[Right tracheal bronchus with anomalous ramification of the bronchial artery disclosed during an episode of hemoptysis].

A 63-year-old woman was referred to our hospital on June 18th, 1998 during an episode of hemoptysis that had lasted for 6 days. She had no hemorrhagic diathesis and no history of pulmonary disease. Chest X-ray films disclosed a ground-glass opacity in the right upper lung field. Bronchoscopic examination revealed bleeding from an anomalous ectopic orifice on the right lateral trachea, about 1 cm above the carina. Chest computed tomographic examinations by conventional and spiral methods readily disclosed an ectopic bronchus. Bronchial arteriography showed that the tracheal bronchus was fed by a branched vessel of the thyrocervical artery arising from the brachiocephalic artery. Atypical mycobacterium was detected in bronchoalveolar lavage fluid from the ectopic bronchus. A shunt had formed with the pulmonary artery and peripheral parts of the bronchial artery that fed the tracheal bronchus. It was speculated that the hemoptysis in this case might be due to the combined phenomena of infection and abnormal vessel formation in the tracheal bronchus. In our patient, the system of blood supply to the tracheal bronchus may have been a manifestation of atavism because it closely resembled the circulatory structure of the tracheal bronchi normally observed in sheep and giraffes. The tracheal bronchus should be taken into consideration as a potential cause of hemoptysis, inflammatory changes, and atelectasis during intubation.

Bronchi↗

Radioimmunoassay for hypocretin-2.

OBJECTIVE: To develop radioimmunoassay for hypocretin-2 (Hcrt-2). And search for its presence in certain rat tissues. METHODS: Anti-Hcrt-2 serum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic Hcrt-2 with bovine serum albumin. Radioiodination of Hcrt-2 was performed by chloramine T method, followed by purification of radoiodinated material on Sephadex G-25 column. RESULTS: The obtained antibody did not cross react with hypocretin-2, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The assay was performed with a double antibody system. Hcrt-2 was extracted from the tissues with acid acetone. The dilution curve of acid acetone extracts of rat hypothalamus in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue Hcrt-2 was about 85 % and the intra-assay and inter-assay variation were 5.6 % and 8.0 %, respectively. Hcrt-2 was found in the hypothalamus, cerebrum, brain stem and testes. CONCLUSIONS: The obtained data suggest that the assay system developed is suitable to measure Hcrt-2 in tissues and that Hcrt-2 is mainly found in the hypothalamus.

Animals↗

[Treatment of acute promyelocytic leukemia with all-trans retinoic acid and chemotherapy--multicenter trial of the Japan Adult Leukemia Study Group (JALSG)].

We report herein the clinical results of a multicenter trial of the Japan Adult Leukemia Study Group for cases of newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy (JALSG AML-92 study). Of 196 evaluable patients, 173 (88%) achieved complete remission (CR). Multivariate analysis showed that no or minor purpura at diagnosis and age less than 30 years were favorable factors for achievement of CR. There was a significant difference in the 4-year event-free survival between the AML-92 study (54%) and both the AML-87 (32%) and AML-89 (32%) studies which consisted of intensive chemotherapy. Since prognosis in patients with APL largely depends on chemotherapy, it is important to consider more effective chemotherapy during induction and consolidation therapy.

Aclarubicin↗